Soluble interleukin 2 receptor molecules in the serum of patients with autoimmune diseases

doi:10.1016/0090-1229(89)90140-2

Clinical Immunology and Immunopathology

Volume 50, Issue 3, March 1989, Pages 321-332

Clinical Immunology ...

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Abstract

Lymphocytes upon activation release a soluble form of interleukin 2 receptor (IL-2R). Systemic autoimmune disorders are characterized by immune system disregulation associated with cellular activation; therefore we sought to determine the levels of soluble IL-2R molecules in the serum of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and primary Sjogren's syndrome (1°SS). Utilizing an enzyme immunoassay method we found increased serum levels of soluble IL-2R in 65.4% ( $3452$ ) of RA, in 34.9% ( $1543$ ) of SLE, and in 25.0% ( $1352$ ) of 1°SS patients, compared to 4.2% ( $124$ ) of healthy individuals. High serum levels of soluble IL-2R correlated with several indices of disease activity in RA and SLE pateints, as well as with disease progression to extraglandular involvement and to pseudolymphoma or lymphoma in patients with 1°SS. By gel filtration analysis, the soluble IL-2R circulating in the serum of a RA patient corresponded to a high molecular weight molecule (>90 kDa) compared to the 65-kDa soluble IL-2R molecule released by phytohemagglutinin-stimulated normal peripheral lymphocytes.

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Citation Excerpt :
Interleukin-2 receptor (IL-2R) is expressed on the membrane of activated mononuclear cells, and the soluble form of IL-2R is released from these cells.1 The level of soluble IL-2R (sIL-2R) reflects inflammation, and is known to be elevated in many conditions such as autoimmune disease, infectious disease, and carcinoma.2-5 A high elevation of sIL-2R is specifically observed in patients with malignant lymphoma, mostly derived from deregulated expression of IL-2R in lymphoma cells.6,7
Although sIL-2R level has a prognostic value in patients with diffuse large B-cell lymphoma, its clinical role in patients with follicular lymphoma has not been determined.
We reviewed data on 70 patients diagnosed with follicular lymphoma.
Ann Arbor stage was I, II, III, and IV in 6, 9, 17, and 38 patients, respectively, and grade classification according to the World Health Organization criteria was 1, 2, 3A, 3B, and not available in 28, 15, 11, 4, and 12 patients, respectively. sIL-2R at diagnosis was significantly correlated with Ann Arbor stages (P < .001), number of nodal lesions (≥ 5 or not) (P = .0050), and Follicular Lymphoma International Prognosis Index risk classification (P = .0015). Furthermore, sIL-2R regressed significantly in patients who achieved complete remission, uncertain complete remission, or partial remission (P < .001), and increased when regrowth of lymphoma was shown (P < .001). Finally, a high level of sIL-2R at diagnosis was correlated with shorter progression-free survival (P = .018) and time to next treatment (P < .001).
Serum-soluble interleukin-2 receptor is correlated with tumor burden at diagnosis and during the clinical course of therapies in patients with follicular lymphoma, and our data support its usefulness to function as a surrogate marker of tumor progression.
Síndrome de Sjögren primario y linfoproliferación
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The consequences of high serum concentrations of the interleukin (IL)-2 receptor α chain (sIL-2Rα) in several diseases are poorly understood. The objective of this study was to determine the form of sIL-2Rα in burn patients and its biological role. sIL-2Rα was measured in 18 severely burned individuals who received nutritional support with a normal or low fat content. sIL-2Rα was elevated throughout the study and it was notably lower in patients fed a low fat diet. Serum IL-6 and sIL-2Rα significantly correlated (r = 0.74, p < 0.05) in burn patients. The presence of sIL-2Rα was associated with a decrease in DR molecules in the CD2⁻ and CD11b⁺ cells of these patients. Western blot analysis of serum protein with N-terminal or C-terminal specific antibodies indicated that sIL-2Rα represents the extracellular domain of this molecule. Patient serum inhibited specifically murine, but not human IL-2–dependent T-cell proliferation. To determine the significance of sIL-2Rα, recombinant sIL-2Rα was used in different cellular model involving IL-2. sIL-2Rα inhibited natural killer cell activity by 50% in the presence of IL-2. The basal proliferation of peripheral blood mononuclear cells was inhibited by sIL-2Rα, but phytohemagglutinin-induced proliferation was unaffected by this form of receptor. Interferon (INF)-γ production induced by OKT-3 on peripheral blood mononuclear cells was not altered by sIL-2Rα, but IL-2 induced increase in INF-γ production was suppressed. The decreasing production of INF-γ in the presence of IL-4 was significantly increased in the presence of sIL-2Rα in media. These results show that the large amount of sIL2-Rα circulating in burn patients is related to the inflammatory response. The amount of dietary fat modulates sIL2Rα concentration in burn patients, confirming the beneficial effect of low fat administration after burn trauma. Inhibition of T-cell activation in burn patients is not directly related to sIL-2Rα, although the presence of sIL-2Rα in serum can inhibit some IL-2 mediated response, such as the emergence of TH1 and TH2 cells.
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Salivary and serum concentrations of soluble interleukin-2 receptor (sIL-2R) were studied in a group of patients with Sjögren’s syndrome and a group suffering from dry mouth. Salivary sIL-2R levels was significantly higher (57.9±15.1 vs 16.7±4.7 pg/ml) (p<0.05) in the group of 26 patients with Sjögren’s syndrome than in the dry-mouth group. Both the salivary and the serum sIL-2R of normal controls were below the level of detection. No significantly statistical differences were noted between the concentrations of serum sIL-2R in either abnormal groups. No correlations were found between salivary or serum sIL-2R and the erythrocyte sedimentation rate, C-reactive protein, the presence of various autoantibodies or the focus score from lip biopsies in the group of patients with Sjögren’s syndrome. The results show that, although the salivary sIL-2R does not actually reflect the extent of inflammation, it might have an important role in the diagnosis of Sjögren’s syndrome.
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Regular articleSoluble interleukin 2 receptor molecules in the serum of patients with autoimmune diseases

Abstract

J. Immunol.

Clin. Immunol. Immunopathol.

Arthritis Rheum

Science

J. Exp. Med.

J. Exp. Med.

J. Immunol.

J. Immunol.

J. Clin. Immunol.

Ann. Intern. Med.

Clin. Res.

J. Clin. Oncol.

J. Immunol.

J. Immunol.

Annu. Rev. Immunol.

J. Immunol.

Clin. Immunol. Immunopathol.

Scand. J. Immunol.

Regular article
Soluble interleukin 2 receptor molecules in the serum of patients with autoimmune diseases